Fast-twitch muscle fibers can be converted to slow-twitch muscle fibers (and vice versa), depending on the stimulation pattern. Chronic electrical stimulation of a fast-twitch muscle results in the expression of slow-twitch myosin and decreased expression of fast-twitch myosin, along with an increase in oxidative capacity. The mechanism or mechanisms underlying this change in gene expression are unknown, but the change appears to be secondary to an elevation in resting intracellular [Ca++]. The Ca++-dependent phosphatase calcineurin and the transcription factor NFAT have been implicated in this transition from the fast-twitch to the slow-twitch phenotype. Ca++/calmodulin-dependent kinase and the transcription factor MEF2 may also participate in the phenotype transition.
8.
Skeletal muscle fibers atrophy after denervation. Muscle fibers depend on the activity of their motor nerves for maintenance of the differentiated phenotype. Reinnervation by axon growth along the original nerve sheath can reverse these changes. Skeletal muscle has a limited capacity to replace cells lost as a result of trauma or disease. Inhibition of the PI3K/Akt signaling pathways and activation of the FoxO pathway appears to contribute to the decreased rate of protein synthesis and the increased rate of protein degradation (respectively) observed during disuse atrophy. The increased protein degradation during atrophy is attributed to increases in both protease activity (e.g., activation of caspase 3) and ubiquitination (through elevated levels of ubiquitin ligases).
9.
Skeletal muscle exhibits considerable phenotypic plasticity. Normal growth is associated with cellular hypertrophy, caused by the addition of more myofibrils and more sarcomeres at the ends of the cell to match skeletal growth. Strength training induces cellular hypertrophy, whereas endurance training increases the
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oxidative capacity of all involved motor units. Training regimens cannot alter fiber type or the expression of myosin isoforms.
10.
Muscle fatigue during exercise is not due to depletion of ATP. The mechanism or mechanisms underlying exercise-induced fatigue are not known, although the accumulation of various metabolic products (lactate, Pi, ADP) has been implicated. In view of the importance of preventing depletion of myoplasmic ATP, which would affect the viability of the cell, it is likely that multiple mechanisms may have been developed to induce fatigue and hence lower the rate of ATP hydrolysis before the individual risks injury or death of the skeletal muscle cell.
11.
When the energy demands of an exercising muscle cannot be met by oxidative metabolism, an oxygen debt is incurred. Increased breathing during the recovery period after exercise reflects this oxygen debt. The greater the reliance on anaerobic metabolism to meet the energy requirements of muscle contraction, the greater the oxygen debt.